In vitro and in vivo biological activity screening of Ru(III) complexes involving 6-benzylaminopurine derivatives with higher pro-apoptotic activity than NAMI-A

A series of novel octahedral ruthenium(III) complexes involving 6-benzylaminopurine (L) derivatives as N-donor ligands has been prepared by the reaction of [(DMSO)2H][trans-RuCl4(DMSO)2] with the corresponding L derivative. The complexes 1–12 have the general compositions trans-[RuCl4(DMSO)(n-Cl-LH)] ⋅ xSol (1–3), trans-[RuCl4(DMSO)(n-Br-LH)] · xSol (4–6), trans-[RuCl4(DMSO)(n-OMe-LH)] · xSol (7–9) and trans-[RuCl4(DMSO)(n-OH-LH)] · xSol (10–12); n = 2, 3, and 4, x = 0–1.5; and Sol = H2O, DMSO, EtOH and/or (Me)2CO. The complexes have been thoroughly characterized by elemental analysis, UV–visible, FTIR, Raman, and EPR spectroscopy, ES + (positive ionization electrospray) mass spectrometry, thermal analysis, cyclic voltammetry, magnetic and conductivity measurements. The X-ray molecular structure of trans-[RuCl4(DMSO)(3-Br-LH)] ⋅ (Me)2CO (5) revealed the distorted octahedral coordination in the vicinity of the central atom, and also confirmed that the 3-Br-L ligand is present as the N3-protonated N7-H tautomer and is coordinated to Ru(III) through the N9 atom of the purine moiety. The tested complexes have been found to be in vitro non-cytotoxic against K562, G361, HOS and MCF7 human cancer cell lines with IC50 > 100 μM in contrast to the moderate results regarding the antiradical activity with IC50 ≈ 10− 3 M. On the contrary, in vivo antitumor activity screening showed that the prepared Ru(III) complexes possess higher pro-apoptotic activity than NAMI-A. The reduction of Ru(III) to Ru(II) and Ru(II)-species formation in tumor tissues was confirmed by means of a simple method of detection and visualization of intracellular Ru(II) by fluorescence microscopy. The originality of this method is based on the preparation of a Ru(II)-bipyridine complex in situ.

Trans-[RuIIICl4(DMSO)(H+L)] complexes involving 6-benzylaminopurine derivatives (L) have been prepared and characterized. The complexes have been found in vitro non-cytotoxic against K562, G361, HOS and MCF7 human cancer cell lines contrary to their moderate antiradical activity. In vivo antitumor activity screening showed that the complexes possess higher pro-apoptotic activity than NAMI-A.Figure optionsDownload as PowerPoint slide